This document was published more than 2 years ago. The nature of the evidence may have changed.
Summary and Conclusions
Technology and target group
Nearly 140 000 patients in Sweden are treated with oral anticoagulants (antithrombotic drugs), specifically vitamin K antagonists (AVK). These drugs attenuate the ability of the blood to coagulate and are used to prevent blood clots. Warfarin is the most commonly used AVK drug in Sweden.
Sensitivity to AVK drugs varies by individual. Even in a single individual, sensitivity varies over time and is influenced, eg, by diet and other drugs. Hence, thorough and regular control of individual treatment intensity is required. Inappropriate dosage increases the risk for complications. If dosage is too low, the risk increases for blood clot formation, while an excessively high dose may cause bleeding. In Sweden, specialized clinics or primary care services manage anticoagulant therapy by analyzing blood samples.
Portable, easy-to-use analytical instruments are now available to check blood coagulation. These systems can be used for both self-testing and self-management. In self-testing, patients perform the test by taking a blood sample via a finger prick and report the results to a clinic. Healthcare staff then set the drug dosage based on values reported by the patient. In self-management, patients not only perform the test, but also set the drug dosage on their own. Before self-testing or self-management can begin, the patient must complete a training program. Healthcare staff also need to be educated to arrange and carry out patient education. Furthermore, healthcare staff must have the skills to manage quality control in the long term through followup and assessment.
In Sweden, the use of self-testing/self-management is limited, with an estimated 800 users. Based on a literature review and a questionnaire to staff of specialized services for anticoagulant treatment and primary health care, an estimated 10% to 20% of all patients treated with AVK drugs may be candidates for self-management in Sweden. This corresponds to between 15 000 and 25 000 patients.
What are the benefits of self-testing and self-management compared to using conventional management (testing and dosing at healthcare facilities) for patients needing long-term treatment with AVK drugs? What risks are associated with the different methods? The aim is also to compare the methods in terms of quality of life and cost-effectiveness.
The assessment included 12 randomized controlled trials (RCTs) that compared self-management to conventional management. In these RCTs, quality and internal validity were rated as high in 2 trials, medium in 3 trials, and low in 7 trials. Three studies on self-testing alone were included, whereof quality and internal validity were rated as medium in 1 study and low in 2 studies.
Results from the literature review suggest that self-management is at least as safe as conventional management in a selected sample of patients. The studies lasted between 3 and 38 months, with an average length of 12 months. Mortality and the prevalence of blood clots and serious bleeding were the main effect measures used in this assessment. Meta-analyses of the studies included show a lower prevalence of thromboembolism during self-management compared to conventional management. The prevalence of serious bleeding, however, did not differ between the groups.
Mortality, including all causes of death, was lower in the self-management group. However, the design of the studies differed, creating some uncertainty in interpreting the results of the meta-analyses.
Since conventional management in Sweden is generally of higher quality than conventional management in most of the studies reviewed, some uncertainty exists as to whether the findings are fully applicable to Swedish conditions.
The main benefit of self-management is an improved quality of life for some patients, eg, they are more independent from health services. Conditions for successful treatment outcomes are that patients have the ability to manage the necessary devices and that they comply with the self-management training program. Hence, individual assessments regarding motivation and appropriateness must be performed.
Long-term followups are lacking, so self-management cannot be evaluated in relation to conventional management in the longer term.
Although self-management requires patients to take greater responsibility for their own treatment, the health services and the attending physician continue to carry responsibility. An important ethical aspect concerns the need for a system to follow up on each patient. If the followup system is inadequate there is a risk that, in the longer term, self-management patients may not continue to regularly check their anticoagulation by blood analysis as needed. It is also important for health services to regularly check on the technical performance of the devices and on how the patients maintain these instruments.
Self-testing devices are not currently subsidized by society, and patients must bear this cost themselves. Hence, not every patient has an equal opportunity to use self-testing/self-management.
Cost estimates based on Swedish conditions indicate that the direct costs for self-management are comparable with, or somewhat higher than, the direct costs for conventional management. Considering the indirect costs of lost productivity, however, self-management could be cost-saving. From a cost-effectiveness standpoint, self-management is more favorable if treatment takes place during an extended period and if the patient’s time represents a high opportunity cost.
SBU’s appraisal of the evidence
Self-management is at least as safe as conventional management for patients who are motivated and can manage the routines on their own (Evidence Grade 1)*. The benefits of self-management for these patients mainly involve improvements in quality of life, eg, greater independence from health services. There is insufficient* scientific evidence to assess self-management in relation to conventional management over the longer term.
There is insufficient* scientific evidence to compare self-testing alone with conventional management.
There is insufficient* scientific evidence to assess the respective cost-effectiveness of self-testing and self-management.
*Criteria for Evidence Grading SBU’s Conclusions
Evidence Grade 1 – Strong Scientific Evidence. The conclusion is corroborated by at least two independent studies with high quality and internal validity, or a good systematic overview.
Evidence Grade 2 – Moderately Strong Scientific Evidence. The conclusion is corroborated by one study with high quality and internal validity, and at least two studies with medium quality and internal validity.
Evidence Grade 3 – Limited Scientific Evidence. The conclusion is corroborated by at least two studies with medium quality and internal validity.
Insufficient Scientific Evidence – No conclusions can be drawn when there are not any studies that meet the criteria for quality and internal validity.
Contradictory Scientific Evidence – No conclusions can be drawn when there are studies with the same quality and internal validity whose findings contradict each other.
This summary is based on a report prepared at SBU in collaboration with Prof. Tomas Lindahl, Linköping University Hospital, Linköping and Assoc. Prof. Peter Svensson, Malmö University Hospital, Malmö. It has been reviewed by Prof. Sam Schulman, McMaster University, Hamilton ON, Canada. Project director: Johan Wallin, SBU.
The complete report is available only in Swedish.
SBU Alert is a service provided by SBU in collaboration with the Medical Products Agency, the National Board of Health and Welfare, and the Swedish Association of Local Authorities and Regions.
- Buller HR, Agnelli G, Hull RD, Hyers TM, Prins MH, Raskob GE. Antithrombotic therapy for venous thromboembolic disease: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004;126(3 Suppl):401S-428S.
- Salem DN, Stein PD, Al-Ahmad A, Bussey HI, Horstkotte D, Miller N et al. Antithrombotic therapy in valvular heart disease – native and prosthetic: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004;126(3 Suppl):457S-482S.
- Singer DE, Albers GW, Dalen JE, Go AS, Halperin JL, Manning WJ. Antithrombotic therapy in atrial fibrillation: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004;126(3 Suppl):429S-456S.
- Weitz JI, Hirsh J, Samama MM. New anticoagulant drugs: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004;126(3 Suppl):265S-286S.
- Hillarp A, Egberg N, Nordin G, Stigendal L, Fagerberg I, Lindahl TL. Local INR calibration of the Owren type prothrombin assay greatly improves the intra- and interlaboratory variation. A three-year follow-up from the Swedish national external quality assessment scheme. Thromb Haemost 2004;91(2):300-7.
- Holbrook AM, Pereira JA, Labiris R, McDonald H, Douketis JD, Crowther M et al. Systematic overview of warfarin and its drug and food interactions. Arch Intern Med 2005;165(10):1095-106.
- Rosendaal FR, Cannegieter SC, van der Meer FJ, Briet E. A method to determine the optimal intensity of oral anticoagulant therapy. Thromb Haemost 1993;69(3):236-9.
- Cannegieter SC, Rosendaal FR, Wintzen AR, van der Meer FJ, Vandenbroucke JP, Briet E. Optimal oral anticoagulant therapy in patients with mechanical heart valves. N Engl J Med 1995;333(1):11-7.
- Hylek EM, Singer DE. Risk factors for intracranial hemorrhage in outpatients taking warfarin. Ann Intern Med 1994;120(11):897-902.
- Oden A, Fahlen M. Oral anticoagulation and risk of death: a medical record linkage study. BMJ 2002;325(7372):1073-5.
- White HD, Gruber M, Feyzi J, Kaatz S, Tse HF, Husted S et al. Comparison of outcomes among patients randomized to warfarin therapy according to anticoagulant control: results from SPORTIF III and V. Arch Intern Med 2007;167(3):239-45.
- Svensk internmedicinsk förening. Verksamhetsuppföljning 2005 för internmedicinska kliniker.
- Karlander S, Lindahl TL. Antikoagulationsbehandling vid de fyra sjukhusen i Östergötland – kvalitetsuppföljning med hjälp av gemensamt datorprogram. Läkartidningen 2002;99(14):1592-4, 1597-8.
- Stigendal L, André U, Christenson B. Bättre AVK-terapi med egenkontroll. Dosen kan justeras i tid. Läkartidningen 1999;96(20):2482, 2485-7.
- Yang DT, Robetorye RS, Rodgers GM. Home prothrombin time monitoring: a literature analysis. Am J Hematol 2004;77(2):177-86.
- Lindahl TL, Egberg N, Hillarp A, Odegaard OR, Edlund B, Svensson J et al. INR calibration of Owren-type prothrombin time based on the relationship between PT% and INR utilizing normal plasma samples. Thromb Haemost 2004;91(6):1223-31.
- Quick A, Stanley-Brown M, Bancroft F. A study of the coagulation defect in hemophilia and jaundice. Am J Med Sci 1935;190:501-11.
- Mattsson C, Menschiek-Lundin A, Wahlander K, Lindahl TL. Effect of melagatran on prothrombin time assays depends on the sensitivity of the thromboplastin and the final dilution of the plasma sample. Thromb Haemost 2001;86(2):611-5.
- Bailleul E, Van Vaerenbergh K, Lust A. Rebuttal to: strong lupus anticoagulant can influence the prothrombin time INR falsifying the follow up of oral anticoagulation. Thromb Haemost 2005;94(3):687; author reply 688.
- Della Valle P, Crippa L, Garlando AM, Pattarini E, Safa O, Vigano D'Angelo S et al. Interference of lupus anticoagulants in prothrombin time assays: implications for selection of adequate methods to optimize the management of thrombosis in the antiphospholipid-antibody syndrome. Haematologica 1999;84(12):1065-74.
- Perry SL, Samsa GP, Ortel TL. Point-of-care testing of the international normalized ratio in patients with antiphospholipid antibodies. Thromb Haemost 2005;94(6):1196-202.
- Skandinavisk Utprövning av Laboratorieutrustning för Primärvården (SKUP). CoaguChek® XS – A system for measurement of prothrombin time [P—PT (INR)] manufactured by Roche Diagnostics. SKUP 2007;55:1-31.
- Arbeitsgemeinschaft Selbstkontrolle der Antikoagulation e.V. (ASA). http://www.asaev.de. 2007.
- Menendez-Jandula B, Souto JC, Oliver A, Montserrat I, Quintana M, Gich I et al. Comparing self-management of oral anticoagulant therapy with clinic management: a randomized trial. Ann Intern Med 2005;142(1):1-10.
- Nilsson C, Svensson P. Kvalitetsuppföljning på antikoagulationsmottagningar i södra sjukvårdsregionen. En kvantitativ empirisk undersökning. Riksstämman 2006:Poster.
- Svensson P. Patient preference and willingness-to-pay among different oral anticoagulant treatment options. The International Society on Thrombosis & Haemostasis (ISTH) XXth Congress 2005:Poster.
- Christensen TD, Maegaard M, Sorensen HT, Hjortdal VE, Hasenkam JM. Self-management versus conventional management of oral anticoagulant therapy: a randomized, controlled trial. Eur J Intern Med 2006;17(4):260-6.
- Cromheecke ME, Levi M, Colly LP, de Mol BJ, Prins MH, Hutten BA et al. Oral anticoagulation self-management and management by a specialist anticoagulation clinic: a randomised cross-over comparison. Lancet 2000;356(9224):97-102.
- Fitzmaurice DA, Murray ET, Gee KM, Allan TF, Hobbs FD. A randomised controlled trial of patient self management of oral anticoagulation treatment compared with primary care management. J Clin Pathol 2002;55(11):845-9.
- Fitzmaurice DA, Murray ET, McCahon D, Holder R, Raftery JP, Hussain S et al. Self management of oral anticoagulation: randomised trial. BMJ 2005;331(7524):1057.
- Gadisseur AP, Breukink-Engbers WG, van der Meer FJ, van den Besselaar AM, Sturk A, Rosendaal FR. Comparison of the quality of oral anticoagulant therapy through patient self-management and management by specialized anticoagulation clinics in the Netherlands: a randomized clinical trial. Arch Intern Med 2003;163(21):2639-46.
- Kortke H, Korfer R. International normalized ratio self-management after mechanical heart valve replacement: is an early start advantageous? Ann Thorac Surg 2001;72(1):44-8.
- Sawicki PT. A structured teaching and self-management program for patients receiving oral anticoagulation: a randomized controlled trial. Working Group for the Study of Patient Self-Management of Oral Anticoagulation. JAMA 1999;281(2):145-50.
- Sidhu P, O'Kane HO. Self-managed anticoagulation: results from a two-year prospective randomized trial with heart valve patients. Ann Thorac Surg 2001;72(5):1523-7.
- Siebenhofer A, Rakovac I, Kleespies C, Piso B, Didjurgeit U. Self-management of oral anticoagulation in the elderly: rationale, design, baselines and oral anticoagulation control after one year of follow-up. A randomized controlled trial. Thromb Haemost 2007;97(3):408-16.
- Sunderji R, Gin K, Shalansky K, Carter C, Chambers K, Davies C et al. A randomized trial of patient self-managed versus physician-managed oral anticoagulation. Can J Cardiol 2004;20(11):1117-23.
- Voller H, Glatz J, Taborski U, Bernardo A, Dovifat C, Heidinger K. Self-management of oral anticoagulation in nonvalvular atrial fibrillation (SMAAF study). Z Kardiol 2005;94(3):182-6.
- Brown A, Wells P, Jaffey J, McGahan L, Poon M-C, Cimon K et al. Point-of-care monitoring devices for long-term oral anticoagulation therapy: clinical and cost effectiveness [Technology report no 72]. Ottawa: Canadian Agency for Drugs and Technologies in Health; 2007.
- Christensen TD, Johnsen SP, Hjortdal VE, Hasenkam JM. Self-management of oral anticoagulant therapy: a systematic review and meta-analysis. Int J Cardiol 2007;118(1):54-61.
- Heneghan C, Alonso-Coello P, Garcia-Alamino JM, Perera R, Meats E, Glasziou P. Self-monitoring of oral anticoagulation: a systematic review and meta-analysis. Lancet 2006;367(9508):404-11.
- Bradburn MJ, Deeks JJ, Berlin JA, Russell Localio A. Much ado about nothing: a comparison of the performance of meta-analytical methods with rare events. Stat Med 2007;26(1):53-77.
- Fitzmaurice DA, Hobbs FD, Murray ET, Holder RL, Allan TF, Rose PE. Oral anticoagulation management in primary care with the use of computerized decision support and near-patient testing: a randomized, controlled trial. Arch Intern Med 2000;160(15):2343-8.
- Beyth RJ, Quinn L, Landefeld CS. A multicomponent intervention to prevent major bleeding complications in older patients receiving warfarin. A randomized, controlled trial. Ann Intern Med 2000;133(9):687-95.
- Khan TI, Kamali F, Kesteven P, Avery P, Wynne H. The value of education and self-monitoring in the management of warfarin therapy in older patients with unstable control of anticoagulation. Br J Haematol 2004;126(4):557-64.
- Gadisseur AP, Kaptein AA, Breukink-Engbers WG, van der Meer FJ, Rosendaal FR. Patient self-management of oral anticoagulant care vs. management by specialized anticoagulation clinics: positive effects on quality of life. J Thromb Haemost 2004;2(4):584-91.
- Socialstyrelsen. Läkemedel – statistik för år 2006. Statistik, Hälso- och sjukvård 2007:1.
- Nilsson GH, Bjorholt I, Johnsson H. Anticoagulant treatment in primary health care in Sweden – prevalence, incidence and treatment diagnosis: a retrospective study on electronic patient records in a registered population. BMC Fam Pract 2003;4:3.
- Reynolds MW, Fahrbach K, Hauch O, Wygant G, Estok R, Cella C et al. Warfarin anticoagulation and outcomes in patients with atrial fibrillation: a systematic review and metaanalysis. Chest 2004;126(6):1938-45.
- Socialstyrelsen. Särskilt utdrag från Läkemedelsregistret för år 2006. 2007.
- Roche Diagnostics. http://www.coaguchek.se. 2007.
- Christensen TD, Maegaard M, Sorensen HT, Hjortdal VE, Hasenkam JM. Self- versus conventional management of oral anticoagulant therapy: effects on INR variability and coumarin dose in a randomized controlled trial. Am J Cardiovasc Drugs 2007;7(3):191-7.
- Claes N, Buntinx F, Vijgen J, Arnout J, Vermylen J, Fieuws S et al. The Belgian Improvement Study on Oral Anticoagulation Therapy: a randomized clinical trial. Eur Heart J 2005;26(20):2159-65.
- Gardiner C, Williams K, Mackie IJ, Machin SJ, Cohen H. Patient self-testing is a reliable and acceptable alternative to laboratory INR monitoring. Br J Haematol 2005;128(2):242-7.
- Horstkotte D, Piper C, Wiemer M. Optimal frequency of patient monitoring and intensity of oral anticoagulation therapy in valvular heart disease. J Thromb Thrombolysis 1998;5 Suppl 1(3):19-24.
- Shiach CR, Campbell B, Poller L, Keown M, Chauhan N. Reliability of point-of-care prothrombin time testing in a community clinic: a randomized crossover comparison with hospital laboratory testing. Br J Haematol 2002;119(2):370-5.
- White RH, McCurdy SA, von Marensdorff H, Woodruff DE Jr, Leftgoff L. Home prothrombin time monitoring after the initiation of warfarin therapy. A randomized, prospective study. Ann Intern Med 1989;111(9):730-7.
presents a comprehensive, systematic assessment of available scientific evidence. The certainty of the evidence for each finding is systematically reviewed and graded. Full assessments include economic, social, and ethical impact analyses.
SBU assessments are performed by a team of leading professional practitioners and academics, patient/user representatives and SBU staff. Prior to approval and publication, assessments are reviewed by independent experts, SBU’s Scientific Advisory Committees and Board of Directors.